steve lafond, pharmd jill wall, bsn, crni · 2017. 4. 20. · anaphylactic and anaphylactoid...
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Anaphylactic andAnaphylactoid Reactions
Steve LaFond, PharmDJill Wall, BSN, CRNI
April 27, 2017
Objectives• Describe anaphylactic and anaphylactoid
reactions• Understand the mechanism of action in
anaphylaxis• Describe the risk factors for developing
anaphylaxis• Describe the clinical manifestations in
anaphylaxis• Identify management of a patient experiencing
anaphylaxis
Approximately 1,500 deaths caused by
anaphylaxis annually in the
U.S.
http://www.tipdisease.com/2013/12/anaphylaxis-causes-symptoms-diagnosis.html
Anaphylaxis Subtypes• Drugs• Latex• Food• Insect stings
Anaphylactic & Anaphylactoid Reactions
• Life-threatening events result from overactive and misdirected immune response to a substance (antigen) that is viewed as foreign to the body.
• Reaction is systemic, involves multiple organ systems, and a direct result of the release of chemical mediators from mast cells and basophils.
Limmer DD., Mistovich JJ., Krost WS. (2004, June 1). Anaphylactic and Anaphylactoid Reactions. EMS World. Retrieved from https://www.cgc.maricopa.edu/Academics/LearningCenter/Writing/Documents/APA_References.pdf.
Anaphylactic & Anaphylactoid Reactions
• Anaphylaxis (allergic reaction)– Requires patient to be sensitized and the
reaction mediated through IgE antibodies– Occurs only after patient has been previously
exposed at least once to antigen and is sensitized
Limmer DD., Mistovich JJ., Krost WS. (2004, June 1). Anaphylactic and Anaphylactoid Reactions. EMS World. Retrieved from https://www.cgc.maricopa.edu/Academics/LearningCenter/Writing/Documents/APA_References.pdf.
Anaphylactic & Anaphylactoid Reactions
• Anaphylactoid reaction (nonallergic reaction)– Does not need presence of IgE antibodies.
Substances initiating the reaction cause a direct breakdown of the mast cell and basophil membranes (e.g., radiopaque contrast media, blood products [e.g., IVIG], NSAIDs, aspirin)
– Can occur following a single, first-time exposure to certain agents in nonsensitized patients
• Both produce same clinical manifestations and treated exactly the same.
Limmer DD., Mistovich JJ., Krost WS. (2004, June 1). Anaphylactic and Anaphylactoid Reactions. EMS World. Retrieved from https://www.cgc.maricopa.edu/Academics/LearningCenter/Writing/Documents/APA_References.pdf.
World Allergy Organization
• Recommends replacing anaphylaxis and anaphylactoid with immunologic anaphylaxis (IgE-mediated and non-IgE mediated [IgG and immune complex complement-mediated]) and nonimmunologic anaphylaxis (events resulting in sudden mast cell & basophil degranulation in the absence of immunoglobulins), respectively.
Shahzad Mustafa, S., Kaliner Michael A., et al. (2017, Feb 22). Anaphylaxis. Retrieved from http://emedicine.medscape.com/article/135065-overview
Mechanisms of Action
Mechanisms of Action (Anaphylaxis)
• Sensitization– An immunologic process that occurs when the
body views a substance as foreign. – In response, IgE antibodies are produced to
fight off the substance. – IgE antibodies have a strong affinity for mast
cells and basophils and attach to receptors on the cell membrane.
Mechanisms of Action (Anaphylaxis)
• Mast cells– Located in connective tissue, near blood vessels,
in mucosal layer in lungs, and GI tract. Filled with granules that release chemical mediators (e.g., histamine, heparin, proteases, chemokines, cytokines).
• Basophils– Contain granules and are polymorphonuclear
leukocytes that circulate in blood; become mast cells
Mechanisms of Action (Anaphylaxis)
• Patient becomes sensitized when IgE antibodies attach to mast cells and basophils.
• IgE antibodies can stay attached for seconds, minutes, days, weeks, months, or years.
Anaphylactic Reaction
http://healthlifemedia.com/healthy/what-is-anaphylaxis
Mechanisms of Action (Anaphylaxis)
• With reintroduction of the antigen in a sensitized patient, it attaches to IgE antibodies located on the cell membranes of the mast cells and basophils.
• This linkage causes breakdown or degranulation of cell membranes, releasing chemical mediators from the cell granules into extracellular fluid.
• These chemical mediators are responsible for producing the clinical condition found in anaphylaxis.
Mechanisms of Action (Anaphylaxis)
• Histamine ➜ Vasodilation, hypotension (increased vascular permeability), flushing, bronchospasm, pruritus, and rhinorrhea
• Leukotrienes ➜ Antihistamine-resistant bronchoconstriction
• Prostaglandins/Thromboxanes ➜ Vasoactive compounds causing bronchoconstriction
Mechanism of Action (Anaphylactoid)
• Complement-mediated by an antigen-antibody complex
• Byproducts of complement cascade (C3a and C5a) and substances called anaphylatoxins
• Cause mast cell and/or basophil degranulation
• Similar systemic manifestations as IgE-mediated anaphylaxis (thus treated in the same manner)
Major Pathophysiologic Factors
• Most signs & symptoms of anaphylaxis are related to:– Increase in vascular permeability– Vasodilatation– Bronchiole smooth muscle contraction (mostly
histamine-mediated)
Risk Factors
Risk Factors• Atopy
– Genetic tendency to develop allergic diseases
• Pre-existing allergies– Foods, drugs, bee stings, environmental allergies
• Female• Older age• Previous exposure to drug• Newly diagnosed, untreated patient• Circulating lymphocyte counts of ≥25,000
Risk Factors• Hematologic malignancies• Route, dosing interval, duration of therapy• Presence of nonhuman sequences (foreign
compounds)• Complex chemical structures (e.g., proteins)• Albumin, enzyme replacement• High-molecular weights (>6000 daltons)• Dextran, Humira®, Remicade®
Risk Factors• Haptens/aggregates (e.g., antibiotics)• Variety of chemicals
– Drugs, food, perfume
• Lack of endogenous proteins• Bee stings, venoms
Clinical Manifestations
Signs & Symptoms of Anaphylaxis
https://en.wikipedia.org/wiki/Anaphylaxis
Clinical Manifestations• Cardiovascular
– Chest pain, palpitations, hypotension, syncope, hypertension, tachycardia, bradycardia, arrhythmia, edema, ischemia or infarction, cardiac arrest
• Central nervous system– Headache, (throbbing), dizziness, anxious,
confusion, altered mental status, level of consciousness (LOC)
Clinical Manifestations• Skin or mucous membranes (80%–90% cases)• Children may present more commonly with
respiratory symptoms followed by cutaneous• Some of most severe cases of anaphylaxis
present in absence of skin findings• Symptoms range from mild dermatologic
complaints to anaphylactic shock to death
Clinical Manifestations• Dermatologic
– Rash, pruritus, urticaria, flushing, local or diffuse erythema, conjunctival erythema and tearing, angioedema, warmth
• Endocrine– Rigors, diaphoresis, fever, generalized feeling of
warmth
Clinical Manifestations• Gastrointestinal
– Nausea, vomiting, metallic taste, diarrhea, abdominal cramping, bloating, dysphagia
• Genitourinary– Incontinence, uterine cramping or pelvic pain,
renal impairment
• Psychiatric– Anxiety, sense of impending doom
Clinical Manifestations• Respiratory
– Cough, dyspnea, nasal congestion, rhinitis, sneezing, hoarseness, tachypnea, wheezing, chest tightness, hypoxemia, bronchospasm, reduced pulmonary expiratory flow, oropharyngeal or laryngeal edema, stridor, pulmonary infiltrates, cyanosis, acute respiratory distress syndrome
AnaphylaxisClinical Syndrome
http://www.priory.com/med/adrenaline.htm
Management of Reaction
Management of Reaction• Emergency care• Support vital functions while eliminating
three primary factors:– Vasodilatation– Increased vascular permeability– Bronchoconstriction
Management of Reaction• Late-phase or biphasic anaphylaxis can occur
up to 72 hours following initial reaction (most occur within 8 to 10 hours)
• Potential risk factors include severity of initial phase, delayed or suboptimal epinephrine dose(s) during initial phase, laryngeal edema, or hypotension during initial phase
• Incidence varies from <1% up to 23% of cases
http://www.australianallergycentre.com.au/anaphylaxis-and-the-adrenaline-epipen
WAO Anaphylaxis Guidelines
• “Even a few minutes’ delay can lead to hypoxic-ischemic encephalopathy or death”
• “The importance of having a management protocol cannot be over emphasized because retention of memorized facts and algorithms can be poor in a crisis and there is little to no time to look up information”
http://www.karger.com/Article/PDF/354543
Prompt Initial Treatment• Initial assessment should take less than
1 minute• Any indication of airway, breathing, or
circulation failure should result in administration of epinephrine and calling 911
Assessment• Assess airway, breathing, circulation (ABC)
– LOC/mental status– Vital signs (sudden reduced BP, hypotonia,
collapse, incontinence)
• Observe for sudden cutaneous manifestations– Urticaria, angioedema, erythema, pruritus, hives,
swollen lips-tongue-uvula
Assessment• Auscultate lungs, listening for
stridor/wheezing, SOB– Dysphonia, cough, hoarseness, hypoxemia
• Assess for sudden gastrointestinal symptoms– Cramping, abdominal pain, vomiting
Interventions• Remove exposure to trigger • Assess airway, breathing, circulation• Administer epinephrine, if needed • Call 911• Place patient supine with legs elevated• Maintain patent airway (O2, high flow, prn)• Maintain IV with 0.9% NS
Interventions• CPR, if indicated• At frequent/regular interval, monitor BP,
HR and function, respiratory status, and oxygenation – Monitor continuously, if possible
Interventions• Obtain VS every 2 minutes until stable• Administer medications, as needed• Provide emotional support to patient/family• Keep patient warm• Stay with patient• Transport via ambulance to hospital
Epinephrine
EpinephrineWAO Guidelines
• “The evidence base for prompt epinephrine injection in the initial treatment of anaphylaxis is stronger than the evidence base for the use of antihistamines and glucocorticoids in anaphylaxis.”
http://www.waojournal.org/content/4/2/13
Epinephrine• Mixed adrenergic agonist (alpha & beta)• Alpha-1 adrenergic vasoconstrictor effect in
most body organ systems• Prevent and relieve airway obstruction
caused by mucosal edema (mediated by beta-2 receptor activity)
• Prevent and relieve hypotension and shock• Mitigates anaphylactic response indirectly
via cAMP second messenger system
Epinephrine• Inject IM as soon as anaphylaxis is
diagnosed or strongly suspected• Dose 0.01 mg/kg of a 1:1,000 (1 mg/ml)
solution to a maximum of 0.5 mg in adults (0.3 mg in children)
• Depending on severity and response to initial injection, dose can be repeated every 5–15 minutes, as needed
Epinephrine• Transient pharmacologic effects
– Pallor, tremor, anxiety, palpitations, dizziness, headache
• Serious adverse effects– Ventricular arrhythmias, hypertensive crisis,
pulmonary edema
Epinephrine Administration Devices
www.auvi-q.com www.epipen.com
www.my-generic-epinephrine-auto-injector.com/en
www.epinephrineautoinject.com
https://www.foodallergy.org/treating-an-allergic-reaction/epinephrine
Epinephrine• American Academy of Pediatrics
recommends epinephrine as a first-line therapy for anaphylaxis
• Update on Meridian’s voluntary worldwide recall of EpiPen® auto-injector– See http://www.mylan.com/epipenrecall
- Frellick M. (2017, Feb. 13). AAP Updates Guidance on Epinephrine Use for Anaphylasix. Medscape. Retrieved from http://www.medscape.com/viewarticle/875689- http://www.mylan.com/epipenrecall
Other Medications
Glucocorticoids• Some effect on early phase reactions of
anaphylaxis, but mostly on mitigating late-phase reactions (caused by neutrophils and cytokines)
• Block transcription of genes that encode cytokines related to the inflammatory pathway
• Given orally (typically prednisone) for less severe reactions or IV (hydrocortisone or methylprednisolone)
Antihistamines (H1 & H2)• Not drug of choice for “initial anaphylaxis
treatment” • Relieves life-threatening respiratory symptoms
or shock• Decreases urticaria, pruritus, vascular
permeability• IV route can cause hypotension if
administered too rapidly• Diphenhydramine (H1 antagonist) drug-of-
choice dosed at 1 mg/kg up to 50 mg
Antihistamines (H1 & H2)• Diphenhydramine
– Can be given IM or IV for treatment, or PO if given as a premedication
• Hydroxyzine or cetirizine– Given PO as a premedication
• H2 antagonists (e.g., cimetidine or ranitidine)– Can be given for more thorough antihistamine
effect
0.9% Normal Saline• Crystalloid solution used to restore
intravascular volume (up to 35% loss due to increased vascular permeability)
• Infuse 1 liter in hypotensive adults or 20 mL/kg in pediatric patients over 15 minutes
Case Studies
Case Study 1• Elaprase® enzyme replacement
– 5-yo with Hunter syndrome (mucopolysaccharidosis II, MPS II)
– Developed initial infusion reaction after several previous infusions w/o reaction
– Symptoms included stridor, wheezing, rigors, fever
– RN stopped infusion/maintained patency of IV– RN administered epinephrine 0.5 mg IM– 911 called and transported to hospital
Case Study 1 (cont.)– Patient recovered and received next 3 infusions
in outpatient short stay– Patient resumed home therapy 4 weeks later and
continued symptom-free for about 4 months– Patient experienced more severe reaction—
cardiorespiratory symptoms including shallow breathing with apneic spells, increased wheezing, hypotension, and bradycardia (from 92 bpm to 55 bpm within 10 minutes)
Case Study 1 (cont.)– Developed mild fever– RN stopped infusion/maintained patency of IV– RN administered epinephrine IM – 911 called– Supported patient in home– MD notified– Patient transported to hospital by ambulance– Patient received infusions in short stay for next
6 months
Case Study 2• IVIG administration (nonclassical S & S)
– Teenage patient with protein-losing enteropathy and immunodeficiency receiving IVIG
– Patient premedicated with ibuprofen and oral Benadryl®
– Patient developed headache, chills, nausea – RN stopped infusion – MD notified– IV diphenhydramine administered, infusion restarted;
tolerated the rest of the infusion– Symptoms resolved post-diphenhydramine
Case Study 2 (cont.)– Next infusion (emesis x1)– Infusion stopped, MD contacted,
IV diphenhydramine administered– Infusion restarted (emesis x1), MD notified,
infusion continued, no further emesis, BP slightly elevated
– IV diphenhydramine—premedicated for future infusions
– No further issues
Case Study 3• IV Zosyn® antibiotic
– 19-yo trached/vented, MRSA/MDRO, tracheobronchitis
– 5 minutes into infusion via Eclipse™ (30-minute infusion), patient developed adverse reaction
– Signs and symptoms• Facial and neck flushing, pruritus, swollen
lips/tongue, SOB, wheezing, hypoxemia, hypotension
Case Study 3 (cont.)– Interventions– Epinephrine administered via EpiPen®
– 911 called– IV diphenhydramine administered– O2 administered– Rapid administration of IV fluids - 0.9% NS– Positioned supine, legs elevated– VS monitored– Patient transported via ambulance– Admitted x 36 hours
Reminder
https://allergies.knoji.com/the-causes-symptoms-and-treatment-of-anaphylactic-shock
Conclusion • Anaphylaxis is a potentially life-threatening
condition.• Anaphylaxis and anaphylactoid reactions
produce the same clinical manifestations and are treated exactly the same.
• Risk factors should be identified in history.
Conclusion • 3 primary factors that result in need for
emergency care:– Vasodilation– Bronchoconstriction– Increased vascular permeability
• Be prepared for rapid implementation of emergency interventions– Any issues with ABC include administration of
epinephrine and calling 911
http://www.covermesongs.com/2013/04/cover-me-qa-whats-your-favorite-cover-song.html
References1. Benjamini, E., Sunshine G., Leskowitz, S. (1996). Immunology: A Short Course, 3rd ed. New York: Wiley.2. Beulow, B., Kaliner, M. (2015, Feb 9). Immediate Hypersensitivity Reactions. Medscape. Retrieved from
http://emedicine.medscape.com/article/136217-overview. 3. Cheng, A. Emergency treatment of anaphylaxis in infants and children. Pediatr Child Health. 2011 Jan; 16(1):
35-40.4. Frellick M. (2017, Feb. 13). AAP Updates Guidance on Epinephrine Use for Anaphylasix. Medscape. Retrieved
from http://www.medscape.com/viewarticle/8756895. Janeway, CA., Travers, P., Walport, M., et al. (2001). Immunobiology: The Immune System in Health and Disease, 5th
edition. New York: Garland Science. 6. Johnson, R., Peebles, R. (2004). Anaphylactic Shock: Pathophysiology, Recognition, and Treatment. Semin Respir
Crit Care Med. 25(6), 695-703.7. Limmer DD., Mistovich JJ., Krost WS. (2004, June 1). Anaphylactic and Anaphylactoid Reactions. EMS World.
Retrieved from https://www.cgc.maricopa.edu/Academics/LearningCenter/Writing/Documents/APA_References.pdf.
8. Rothenberg, M. (2000). Mechanisms of Disease: Pathophysiology A Plain English Approach. Eau Claire, Wisconsin: PESI Healthcare.
9. Shahzad Mustafa, S., Kaliner M., et al. (2017, Feb 22). Anaphylaxis. Medscape. Retrieved from http://emedicine.medscape.com/article/135065-overview.
10. Tang, A. (2003). A Practical Guide to Anaphylaxis. Am Fam Physician. 68(7), 1325-1333.
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